Autophagy and Cellular Senescence in Lung Diseases

Abstract

Autophagy is a process of lysosomal self-degradation that helps maintain homeostatic balance between the synthesis, degradation and recycling of cellular proteins and organelles. In addition to nutrient starvation, a wide array of cellular stresses are also known to be strong inducers of autophagy, indicating that autophagy is not only simple amino acid supply machinery in response to energy demand but also a central component of the integrated stress response for cytoprotection. Since autophagy is an adaptive pathway of cytoprotection from cellular stresses, involving starvation, reactive oxygen species, endoplasmic reticulum stress, and microbe infection, it is reasonable to suggest that autophagy is closely related with aging. Indeed, autophagy diminishes with aging and accelerated aging can be attributed to reduced autophagy. Cellular senescence is also one of the cellular stress responses as well as autophagy, and considered to be one of the processes of aging. Cellular senescence has been widely implicated in disease pathogenesis in terms of not only impaired cell repopulation but also aberrant cytokine secretions of senescence associated secretory phenotype, which may exert deleterious effects on the tissue microenvironment of neighboring cells. The detailed molecular mechanism for regulation of autophagy and cellular senescence is complex and the role of autophagy and cellular senescence is overlap significantly. We review molecular mechanisms of autophagy and cellular senescence, and summarize the role of autophagy and cellular senescence in pulmonary disease pathogeneses.